Hodgkin Disease, Lymphoma, Non-Hodgkin, Neoplasms
Conditions
Brief summary
This study of MK-8776 (SCH 900776) will evaluate its safety and tolerability when given as monotherapy or in combination with gemcitabine to participants with advanced solid tumors or lymphoma. Participants will be enrolled in cohorts that will receive sequentially higher doses of MK-8776 in combination with standard doses of gemcitabine The recommended combination doses for a Phase 2 trial (combination-RP2D) will be determined based on safety and biological activity. Up to 10 to 15 additional participants may be studied at the combination-RP2D.
Interventions
DRUGMK-8776
IV infusion
DRUGGemcitabine
IV infusion
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must have a diagnosis of an advanced solid tumor malignancy or lymphoma (non-Hodgkin's or Hodgkin's lymphoma). * Must have histological or cytological evidence of malignancy. * Must have an advanced malignancy, metastatic or unresectable. For Part A of the study, the metastatic or unresectable malignancy should have recurred or progressed following standard therapy or failed standard therapy; or for which no standard therapy currently exists, or for which they are not candidates for standard therapy. For Parts B and C of the study, participants with advanced tumors for which gemcitabine is considered standard therapy (eg, pancreatic cancer), may be enrolled without having received prior gemcitabine. Standard therapy is defined as therapy that is approved in a particular line of therapy or considered as standard of care based on published peer reviewed data in a specific line of therapy. * Gemcitabine-naïve participants with tumors known to be responsive to gemcitabine or participants previously treated with gemcitabine who did not progress while on treatment or who are currently still responding to treatment should only be enrolled in cohorts for which gemcitabine doses are \>=1000 mg/m². Participants previously treated with gemcitabine, whose disease has progressed wile on treatment, can be enrolled to any part. * Must be ambulatory with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Participants (and/or parent/guardian for participants who otherwise are unable to provide independent consent) must be willing to give written informed consent and able to adhere to dose and visit schedules. * Female participants of childbearing potential must have a negative pregnancy test within 7 days of first dose of protocol therapy. * Female participants of childbearing potential and male participants whose sexual partners are of childbearing potential must agree to abstain from sexual intercourse or to use an acceptable method of contraception during the study and for 90 days following the last dose of protocol therapy. Acceptable methods of contraception include condoms (male or female) with or without spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed intrauterine device (IUD), oral or injectable hormonal contraceptive, and surgical sterilization (eg, hysterectomy or tubal ligation). * Must have adequate bone marrow reserve as evidenced by a white blood cell (WBC) count \>=3,000/ μL, absolute neutrophil count (ANC) \>=1,500/μL AND platelet count \>=100,000/μL. * Must have adequate renal function as evidenced by a serum creatinine level \<=1.5 x upper limit of normal (ULN) or a calculated creatinine clearance \>60 mL/min. * Participants, except those with known Gilbert's Syndrome, must have adequate hepatic function as evidenced by a serum bilirubin level \<=1.5 x the ULN AND serum levels of aspartate and alanine aminotransferase (AST/ALT) levels \<=3 x the ULN for the reference lab (participants with known hepatic metastases must have serum AST/ALT levels \<=5 x the ULN for the reference lab). * Must be recovered from the effects of any prior surgery, radiotherapy or systemic antineoplastic therapy.
Exclusion criteria
* Has a known hypersensitivity to MK-8776 or gemcitabine or to any of their excipients or has received therapy with another Checkpoint kinase 1 (CHK1) inhibitor. * Has received any prohibited medication more recently than the indicated washout period prior to first dose of protocol therapy or must continue to receive prohibited medications. Prohibited medications: cytochrome P450 1A2 inhibitors, any chemotherapy, or investigational drugs. * Has significant underlying cardiac conduction system abnormalities such as bifascicular or greater block (eg, right bundle branch block with left anterior hemiblock or first degree atrioventricular block), fixed-rate pacemaker, or chronic atrial fibrillation with variable ventricular rate. * Has persistent, unresolved Common Terminology Criteria for Adverse Events (CTCAE) v 3.0 \>=Grade 2 drug-related toxicity (except alopecia, erectile impotence, hot flashes, and decreased libido) associated with previous treatment. * Has known human immunodeficiency virus (HIV), hepatitis B, hepatitis C, or a known history of liver cirrhosis or active alcohol abuse. * Is New York Heart Association (NYHA) Class III. * Has any other medical or psychiatric condition that, in the opinion of the investigator, might interfere with the subject's participation in the trial or interfere with the interpretation of trial results. * Has undergone major surgery within 3 weeks prior to first study drug administration after enrollment. * Has central nervous system (CNS) or leptomeningeal metastases. * Has received radiation therapy within 3 weeks prior to first study drug administration after enrollment or radiation therapy to \>25% of bone marrow. * Has received \>3 prior chemotherapy regimens (may have received prior gemcitabine). A participant may not have experienced any CTCAE v 3.0 \>Grade 1 myelotoxicity (neutropenia and/or thrombocytopenia) with any prior regimen, including gemcitabine. Participants with \>3 prior chemotherapy regimens, one or more of which were targeted, nonmyelosuppressive agents, may be considered on a case-by-case basis after discussion with the sponsor. * Has undergone previous allogeneic or autologous stem cell transplant. * Has had any of the following within 6 months prior to first study drug administration after enrollment: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or seizure disorder. * Has a known bleeding diathesis, eg, hemophilia. * Has a baseline QTc interval \>450 msec (ie, CTCAE v 3.0 Grade ≥2) at screening (within 21 days prior to 1st dose of MK-8776, mean of triplicate readings within approximately 5 minutes). * History of risk factors for Torsades de Pointes, including clinical history of heart failure, hypo- or hyperkalemia or hypomagnesemia (supplementation or other appropriate interventions to bring levels within normal institutional limits prior to administration of MK-8776 is acceptable), or family history of Long QT Syndrome. * Currently a smoker and/or is likely to smoke during the study. * Female participant who is breast-feeding, pregnant, or intends to become pregnant. * Participating in any other interventional clinical study. (Participants participating in another noninterventional study may be considered after discussion with the sponsor.) * Part of the staff personnel directly related to this study. * Family member of one of the investigational staff.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced an Adverse Event (AE) | Up to approximately 72 weeks (Up to approximately 6 weeks after last dose of study treatment) | An AE was defined as any untoward medical occurrence in a participant administered study treatment which did not necessarily have to have a causal relationship with this treatment. An AE could have been any unfavorable and unintended sign (e.g. an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to study treatment. The number of participants who experienced an AE is presented. |
| Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) During Cycle 0 and Cycle 1 Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE v 3.0) | Through Cycle 0 and Cycle 1 (Up to 42 days) | During Cycle 0, a DLT was defined as: CTCAE v 3.0 Grade 3 neutropenia or thrombocytopenia lasting ≥3 days; any CTCAE v 3.0 Grade 4 neutropenia or thrombocytopenia; neutropenic fever; any CTCAE v. 3.0 ≥ Grade 3 QT interval corrected by Fridericia (QTcF) prolongation of any duration; any other CTCAE v 3.0 Grade 3 or higher nonhematologic toxicity; or Grade 3 elevation of transaminases that resolved prior to administration of next dose(s) of study drug(s); delay in Cycle 1 Day 1 beyond 3 weeks due to continuing toxicity. During Cycle 1, a DLT was defined as: CTCAE v 3.0 Grade 4 neutropenia that persists for ≥7 days; neutropenic fever; CTCAE v 3.0 Grade 4 thrombocytopenia; CTCAE v 3.0 ≥ Grade 3 thrombocytopenia with bleeding; any CTCAE v 3.0 QTc ≥ Grade 3 QTcF prolongation of any duration; any other CTCAE v 3.0 Grade 3 or higher nonhematologic toxicity; or Grade 3 elevation of transaminases that resolved prior to administration of next dose(s) of study drug(s). |
| Number of Participants Who Discontinued Study Treatment Due to an AE | Up to approximatey 66 weeks | An AE was defined as any untoward medical occurrence in a participant administered study treatment which did not necessarily have to have a causal relationship with this treatment. An AE could have been any unfavorable and unintended sign (e.g. an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to study treatment. The number of participants who discontinued study treatment due to an AE is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MK-8776 Maximum Plasma Concentration (Cmax) | At end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion | The Cmax of MK-8776 was assessed in Cycle 0 and in Cycle 1. On Day 1 of Cycle 0 and Cycle 1, plasma samples were obtained from all participants before infusion, at end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion. |
| MK-8776 Terminal Phase Half-Life (t1/2) | At end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion | The t1/2 of MK-8776 was assessed in Cycle 0 and in Cycle 1. On Day 1 of Cycle 0 and Cycle 1, plasma samples were obtained from all participants before infusion, at end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion. |
| MK-8776 Area Under the Curve of the Plasma Concentration Versus Time From Time Zero to the Time of the Last Analytically Quantifiable Concentration (AUC0-last) | At end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion | AUC0-last was assessed in Cycle 0 and in Cycle 1. On Day 1 of Cycle 0 and Cycle 1, plasma samples were obtained from all participants before infusion, at end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion. AUC0-last was calculated by the linear trapezoidal method. |
| Time of MK-8776 Cmax (Tmax) | At end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion | The time of Cmax of MK-8776 was assessed in Cycle 0 and in Cycle 1. On Day 1 of Cycle 0 and Cycle 1, plasma samples were obtained from all participants before infusion, at end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MK-8776 10mg/m^2+Gemcitabine 800mg/m^2 Participants received MK-8776 10 mg/m\^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m\^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. | 3 |
| MK-8776 20mg/m^2+Gemcitabine 800mg/m^2 Participants received MK-8776 20 mg/m\^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m\^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. | 3 |
| MK-8776 40mg/m^2+Gemcitabine 800mg/m^2 Participants received MK-8776 40 mg/m\^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m\^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. | 7 |
| MK-8776 80mg/m^2+Gemcitabine 800mg/m^2 Participants received MK-8776 80 mg/m\^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m\^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. | 6 |
| MK-8776 112mg/m^2+Gemcitabine 800mg/m^2 Participants received MK-8776 112 mg/m\^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m\^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. | 7 |
| MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2 Participants received MK-8776 80 mg/m\^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m\^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. | 6 |
| MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2 Participants received MK-8776 112 mg/m\^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m\^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. | 8 |
| MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2 Participants received MK-8776 150 mg/m\^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m\^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. | 3 |
| MK-8776 200mg+Gemcitabine 1000mg/m^2 Participants received MK-8776 200 mg given as a flat dose monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m\^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. | 2 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 2 | 0 | 0 | 0 | 2 | 1 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Ongoing in Study | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 |
| Overall Study | Progression of Disease | 0 | 1 | 2 | 6 | 5 | 1 | 4 | 2 | 1 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Symptomatic Deterioration | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 2 | 0 | 0 | 2 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | MK-8776 10mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 20mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 40mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 80mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 112mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2 | MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2 | MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2 | MK-8776 200mg+Gemcitabine 1000mg/m^2 | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 54.3 Years STANDARD_DEVIATION 16 | 54.3 Years STANDARD_DEVIATION 8.6 | 64.0 Years STANDARD_DEVIATION 16.1 | 55.5 Years STANDARD_DEVIATION 5 | 51.1 Years STANDARD_DEVIATION 5.7 | 59.0 Years STANDARD_DEVIATION 13.4 | 59.9 Years STANDARD_DEVIATION 9.1 | 69.3 Years STANDARD_DEVIATION 5.5 | 69.0 Years STANDARD_DEVIATION 8.5 | 58.8 Years STANDARD_DEVIATION 11.2 |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 2 Participants | 2 Participants | 4 Participants | 2 Participants | 3 Participants | 1 Participants | 2 Participants | 18 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 5 Participants | 4 Participants | 3 Participants | 4 Participants | 5 Participants | 2 Participants | 0 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 7 / 7 | 6 / 6 | 7 / 7 | 4 / 4 | 8 / 8 | 3 / 3 | 2 / 2 |
| serious Total, serious adverse events | 2 / 3 | 1 / 3 | 3 / 7 | 1 / 6 | 2 / 7 | 3 / 4 | 4 / 8 | 0 / 3 | 2 / 2 |
Outcome results
Primary
Number of Participants Who Discontinued Study Treatment Due to an AE
An AE was defined as any untoward medical occurrence in a participant administered study treatment which did not necessarily have to have a causal relationship with this treatment. An AE could have been any unfavorable and unintended sign (e.g. an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to study treatment. The number of participants who discontinued study treatment due to an AE is presented.
Time frame: Up to approximatey 66 weeks
Population: The population consisted of all participants who received at least one dose of MK-8776.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-8776 10mg/m^2+Gemcitabine 800mg/m^2 | Number of Participants Who Discontinued Study Treatment Due to an AE | 1 Participants |
| MK-8776 20mg/m^2+Gemcitabine 800mg/m^2 | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| MK-8776 40mg/m^2+Gemcitabine 800mg/m^2 | Number of Participants Who Discontinued Study Treatment Due to an AE | 2 Participants |
| MK-8776 80mg/m^2+Gemcitabine 800mg/m^2 | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| MK-8776 112mg/m^2+Gemcitabine 800mg/m^2 | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2 | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2 | Number of Participants Who Discontinued Study Treatment Due to an AE | 2 Participants |
| MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2 | Number of Participants Who Discontinued Study Treatment Due to an AE | 1 Participants |
| MK-8776 200mg+Gemcitabine 1000mg/m^2 | Number of Participants Who Discontinued Study Treatment Due to an AE | 1 Participants |
Primary
Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) During Cycle 0 and Cycle 1 Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE v 3.0)
During Cycle 0, a DLT was defined as: CTCAE v 3.0 Grade 3 neutropenia or thrombocytopenia lasting ≥3 days; any CTCAE v 3.0 Grade 4 neutropenia or thrombocytopenia; neutropenic fever; any CTCAE v. 3.0 ≥ Grade 3 QT interval corrected by Fridericia (QTcF) prolongation of any duration; any other CTCAE v 3.0 Grade 3 or higher nonhematologic toxicity; or Grade 3 elevation of transaminases that resolved prior to administration of next dose(s) of study drug(s); delay in Cycle 1 Day 1 beyond 3 weeks due to continuing toxicity. During Cycle 1, a DLT was defined as: CTCAE v 3.0 Grade 4 neutropenia that persists for ≥7 days; neutropenic fever; CTCAE v 3.0 Grade 4 thrombocytopenia; CTCAE v 3.0 ≥ Grade 3 thrombocytopenia with bleeding; any CTCAE v 3.0 QTc ≥ Grade 3 QTcF prolongation of any duration; any other CTCAE v 3.0 Grade 3 or higher nonhematologic toxicity; or Grade 3 elevation of transaminases that resolved prior to administration of next dose(s) of study drug(s).
Time frame: Through Cycle 0 and Cycle 1 (Up to 42 days)
Population: The population consisted of all participants who were evaluable for DLT assessment (i.e., completed Cycle 0 and Cycle 1).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-8776 10mg/m^2+Gemcitabine 800mg/m^2 | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) During Cycle 0 and Cycle 1 Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE v 3.0) | 0 Participants |
| MK-8776 20mg/m^2+Gemcitabine 800mg/m^2 | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) During Cycle 0 and Cycle 1 Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE v 3.0) | 0 Participants |
| MK-8776 40mg/m^2+Gemcitabine 800mg/m^2 | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) During Cycle 0 and Cycle 1 Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE v 3.0) | 1 Participants |
| MK-8776 80mg/m^2+Gemcitabine 800mg/m^2 | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) During Cycle 0 and Cycle 1 Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE v 3.0) | 0 Participants |
| MK-8776 112mg/m^2+Gemcitabine 800mg/m^2 | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) During Cycle 0 and Cycle 1 Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE v 3.0) | 2 Participants |
| MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2 | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) During Cycle 0 and Cycle 1 Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE v 3.0) | 0 Participants |
| MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2 | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) During Cycle 0 and Cycle 1 Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE v 3.0) | 1 Participants |
| MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2 | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) During Cycle 0 and Cycle 1 Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE v 3.0) | 0 Participants |
| MK-8776 200mg+Gemcitabine 1000mg/m^2 | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) During Cycle 0 and Cycle 1 Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE v 3.0) | 0 Participants |
Primary
Number of Participants Who Experienced an Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered study treatment which did not necessarily have to have a causal relationship with this treatment. An AE could have been any unfavorable and unintended sign (e.g. an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to study treatment. The number of participants who experienced an AE is presented.
Time frame: Up to approximately 72 weeks (Up to approximately 6 weeks after last dose of study treatment)
Population: The population consisted of all participants who received at least one dose of MK-8776.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-8776 10mg/m^2+Gemcitabine 800mg/m^2 | Number of Participants Who Experienced an Adverse Event (AE) | 3 Participants |
| MK-8776 20mg/m^2+Gemcitabine 800mg/m^2 | Number of Participants Who Experienced an Adverse Event (AE) | 3 Participants |
| MK-8776 40mg/m^2+Gemcitabine 800mg/m^2 | Number of Participants Who Experienced an Adverse Event (AE) | 7 Participants |
| MK-8776 80mg/m^2+Gemcitabine 800mg/m^2 | Number of Participants Who Experienced an Adverse Event (AE) | 6 Participants |
| MK-8776 112mg/m^2+Gemcitabine 800mg/m^2 | Number of Participants Who Experienced an Adverse Event (AE) | 7 Participants |
| MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2 | Number of Participants Who Experienced an Adverse Event (AE) | 4 Participants |
| MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2 | Number of Participants Who Experienced an Adverse Event (AE) | 8 Participants |
| MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2 | Number of Participants Who Experienced an Adverse Event (AE) | 3 Participants |
| MK-8776 200mg+Gemcitabine 1000mg/m^2 | Number of Participants Who Experienced an Adverse Event (AE) | 2 Participants |
Secondary
MK-8776 Area Under the Curve of the Plasma Concentration Versus Time From Time Zero to the Time of the Last Analytically Quantifiable Concentration (AUC0-last)
AUC0-last was assessed in Cycle 0 and in Cycle 1. On Day 1 of Cycle 0 and Cycle 1, plasma samples were obtained from all participants before infusion, at end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion. AUC0-last was calculated by the linear trapezoidal method.
Time frame: At end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion
Population: The population consisted of all participants who received at least two cycles of study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MK-8776 10mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 Area Under the Curve of the Plasma Concentration Versus Time From Time Zero to the Time of the Last Analytically Quantifiable Concentration (AUC0-last) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 565 ng*hr/mL | Standard Deviation 171 |
| MK-8776 10mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 Area Under the Curve of the Plasma Concentration Versus Time From Time Zero to the Time of the Last Analytically Quantifiable Concentration (AUC0-last) | Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2) | 539 ng*hr/mL | Standard Deviation 307 |
| MK-8776 20mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 Area Under the Curve of the Plasma Concentration Versus Time From Time Zero to the Time of the Last Analytically Quantifiable Concentration (AUC0-last) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 1400 ng*hr/mL | Standard Deviation 448 |
| MK-8776 20mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 Area Under the Curve of the Plasma Concentration Versus Time From Time Zero to the Time of the Last Analytically Quantifiable Concentration (AUC0-last) | Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2) | 1570 ng*hr/mL | Standard Deviation 423 |
| MK-8776 40mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 Area Under the Curve of the Plasma Concentration Versus Time From Time Zero to the Time of the Last Analytically Quantifiable Concentration (AUC0-last) | Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2) | 1900 ng*hr/mL | Standard Deviation 859 |
| MK-8776 40mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 Area Under the Curve of the Plasma Concentration Versus Time From Time Zero to the Time of the Last Analytically Quantifiable Concentration (AUC0-last) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 2250 ng*hr/mL | Standard Deviation 948 |
| MK-8776 80mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 Area Under the Curve of the Plasma Concentration Versus Time From Time Zero to the Time of the Last Analytically Quantifiable Concentration (AUC0-last) | Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2) | 4540 ng*hr/mL | Standard Deviation 1660 |
| MK-8776 80mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 Area Under the Curve of the Plasma Concentration Versus Time From Time Zero to the Time of the Last Analytically Quantifiable Concentration (AUC0-last) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 5060 ng*hr/mL | Standard Deviation 1920 |
| MK-8776 112mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 Area Under the Curve of the Plasma Concentration Versus Time From Time Zero to the Time of the Last Analytically Quantifiable Concentration (AUC0-last) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 9050 ng*hr/mL | Standard Deviation 5500 |
| MK-8776 112mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 Area Under the Curve of the Plasma Concentration Versus Time From Time Zero to the Time of the Last Analytically Quantifiable Concentration (AUC0-last) | Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2) | 10300 ng*hr/mL | Standard Deviation 6370 |
| MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2 | MK-8776 Area Under the Curve of the Plasma Concentration Versus Time From Time Zero to the Time of the Last Analytically Quantifiable Concentration (AUC0-last) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 4040 ng*hr/mL | Standard Deviation 1010 |
| MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2 | MK-8776 Area Under the Curve of the Plasma Concentration Versus Time From Time Zero to the Time of the Last Analytically Quantifiable Concentration (AUC0-last) | Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2) | 4660 ng*hr/mL | Standard Deviation 815 |
| MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2 | MK-8776 Area Under the Curve of the Plasma Concentration Versus Time From Time Zero to the Time of the Last Analytically Quantifiable Concentration (AUC0-last) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 9240 ng*hr/mL | Standard Deviation 5740 |
| MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2 | MK-8776 Area Under the Curve of the Plasma Concentration Versus Time From Time Zero to the Time of the Last Analytically Quantifiable Concentration (AUC0-last) | Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2) | 6900 ng*hr/mL | Standard Deviation 3120 |
| MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2 | MK-8776 Area Under the Curve of the Plasma Concentration Versus Time From Time Zero to the Time of the Last Analytically Quantifiable Concentration (AUC0-last) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 18500 ng*hr/mL | Standard Deviation 8000 |
| MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2 | MK-8776 Area Under the Curve of the Plasma Concentration Versus Time From Time Zero to the Time of the Last Analytically Quantifiable Concentration (AUC0-last) | Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2) | 13000 ng*hr/mL | — |
| MK-8776 200mg+Gemcitabine 1000mg/m^2 | MK-8776 Area Under the Curve of the Plasma Concentration Versus Time From Time Zero to the Time of the Last Analytically Quantifiable Concentration (AUC0-last) | Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2) | 16900 ng*hr/mL | — |
| MK-8776 200mg+Gemcitabine 1000mg/m^2 | MK-8776 Area Under the Curve of the Plasma Concentration Versus Time From Time Zero to the Time of the Last Analytically Quantifiable Concentration (AUC0-last) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 8440 ng*hr/mL | — |
Secondary
MK-8776 Maximum Plasma Concentration (Cmax)
The Cmax of MK-8776 was assessed in Cycle 0 and in Cycle 1. On Day 1 of Cycle 0 and Cycle 1, plasma samples were obtained from all participants before infusion, at end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion.
Time frame: At end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion
Population: The population consisted of all participants who received at least two cycles of study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MK-8776 10mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 Maximum Plasma Concentration (Cmax) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 414 ng/mL | Standard Deviation 257 |
| MK-8776 10mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 Maximum Plasma Concentration (Cmax) | Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2) | 445 ng/mL | Standard Deviation 249 |
| MK-8776 20mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 Maximum Plasma Concentration (Cmax) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 1010 ng/mL | Standard Deviation 197 |
| MK-8776 20mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 Maximum Plasma Concentration (Cmax) | Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2) | 1650 ng/mL | Standard Deviation 1520 |
| MK-8776 40mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 Maximum Plasma Concentration (Cmax) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 1220 ng/mL | Standard Deviation 366 |
| MK-8776 40mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 Maximum Plasma Concentration (Cmax) | Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2) | 962 ng/mL | Standard Deviation 454 |
| MK-8776 80mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 Maximum Plasma Concentration (Cmax) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 4970 ng/mL | Standard Deviation 1500 |
| MK-8776 80mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 Maximum Plasma Concentration (Cmax) | Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2) | 3700 ng/mL | Standard Deviation 1930 |
| MK-8776 112mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 Maximum Plasma Concentration (Cmax) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 5270 ng/mL | Standard Deviation 3730 |
| MK-8776 112mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 Maximum Plasma Concentration (Cmax) | Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2) | 4710 ng/mL | Standard Deviation 2310 |
| MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2 | MK-8776 Maximum Plasma Concentration (Cmax) | Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2) | 3610 ng/mL | Standard Deviation 2290 |
| MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2 | MK-8776 Maximum Plasma Concentration (Cmax) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 2960 ng/mL | Standard Deviation 1290 |
| MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2 | MK-8776 Maximum Plasma Concentration (Cmax) | Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2) | 4690 ng/mL | Standard Deviation 2610 |
| MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2 | MK-8776 Maximum Plasma Concentration (Cmax) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 6210 ng/mL | Standard Deviation 2160 |
| MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2 | MK-8776 Maximum Plasma Concentration (Cmax) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 6220 ng/mL | Standard Deviation 2550 |
| MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2 | MK-8776 Maximum Plasma Concentration (Cmax) | Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2) | 4940 ng/mL | — |
| MK-8776 200mg+Gemcitabine 1000mg/m^2 | MK-8776 Maximum Plasma Concentration (Cmax) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 4860 ng/mL | — |
| MK-8776 200mg+Gemcitabine 1000mg/m^2 | MK-8776 Maximum Plasma Concentration (Cmax) | Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2) | 3700 ng/mL | — |
Secondary
MK-8776 Terminal Phase Half-Life (t1/2)
The t1/2 of MK-8776 was assessed in Cycle 0 and in Cycle 1. On Day 1 of Cycle 0 and Cycle 1, plasma samples were obtained from all participants before infusion, at end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion.
Time frame: At end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion
Population: The population consisted of all participants who received at least two cycles of study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MK-8776 10mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 Terminal Phase Half-Life (t1/2) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 6.29 hr | Standard Deviation 1.97 |
| MK-8776 10mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 Terminal Phase Half-Life (t1/2) | Cycle 1 (n=3, 3, 6, 6, 7, 4, 7, 1, 2) | 6.24 hr | Standard Deviation 2.03 |
| MK-8776 20mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 Terminal Phase Half-Life (t1/2) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 9.33 hr | Standard Deviation 5.09 |
| MK-8776 20mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 Terminal Phase Half-Life (t1/2) | Cycle 1 (n=3, 3, 6, 6, 7, 4, 7, 1, 2) | 8.57 hr | Standard Deviation 4.54 |
| MK-8776 40mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 Terminal Phase Half-Life (t1/2) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 8.45 hr | Standard Deviation 2.95 |
| MK-8776 40mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 Terminal Phase Half-Life (t1/2) | Cycle 1 (n=3, 3, 6, 6, 7, 4, 7, 1, 2) | 8.23 hr | Standard Deviation 1.71 |
| MK-8776 80mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 Terminal Phase Half-Life (t1/2) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 7.44 hr | Standard Deviation 0.435 |
| MK-8776 80mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 Terminal Phase Half-Life (t1/2) | Cycle 1 (n=3, 3, 6, 6, 7, 4, 7, 1, 2) | 9.01 hr | Standard Deviation 2.51 |
| MK-8776 112mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 Terminal Phase Half-Life (t1/2) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 5.94 hr | Standard Deviation 1.62 |
| MK-8776 112mg/m^2+Gemcitabine 800mg/m^2 | MK-8776 Terminal Phase Half-Life (t1/2) | Cycle 1 (n=3, 3, 6, 6, 7, 4, 7, 1, 2) | 7.29 hr | Standard Deviation 1.26 |
| MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2 | MK-8776 Terminal Phase Half-Life (t1/2) | Cycle 1 (n=3, 3, 6, 6, 7, 4, 7, 1, 2) | 7.87 hr | Standard Deviation 2.11 |
| MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2 | MK-8776 Terminal Phase Half-Life (t1/2) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 8.13 hr | Standard Deviation 1.3 |
| MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2 | MK-8776 Terminal Phase Half-Life (t1/2) | Cycle 1 (n=3, 3, 6, 6, 7, 4, 7, 1, 2) | 7.98 hr | Standard Deviation 1.21 |
| MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2 | MK-8776 Terminal Phase Half-Life (t1/2) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 7.14 hr | Standard Deviation 1.9 |
| MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2 | MK-8776 Terminal Phase Half-Life (t1/2) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 9.46 hr | Standard Deviation 2.11 |
| MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2 | MK-8776 Terminal Phase Half-Life (t1/2) | Cycle 1 (n=3, 3, 6, 6, 7, 4, 7, 1, 2) | 7.59 hr | — |
| MK-8776 200mg+Gemcitabine 1000mg/m^2 | MK-8776 Terminal Phase Half-Life (t1/2) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 6.30 hr | — |
| MK-8776 200mg+Gemcitabine 1000mg/m^2 | MK-8776 Terminal Phase Half-Life (t1/2) | Cycle 1 (n=3, 3, 6, 6, 7, 4, 7, 1, 2) | 9.89 hr | — |
Secondary
Time of MK-8776 Cmax (Tmax)
The time of Cmax of MK-8776 was assessed in Cycle 0 and in Cycle 1. On Day 1 of Cycle 0 and Cycle 1, plasma samples were obtained from all participants before infusion, at end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion.
Time frame: At end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion
Population: The population consisted of all participants who received at least two cycles of study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MK-8776 10mg/m^2+Gemcitabine 800mg/m^2 | Time of MK-8776 Cmax (Tmax) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 0.27 hr | Standard Deviation 0.03 |
| MK-8776 10mg/m^2+Gemcitabine 800mg/m^2 | Time of MK-8776 Cmax (Tmax) | Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2) | 0.26 hr | Standard Deviation 0.01 |
| MK-8776 20mg/m^2+Gemcitabine 800mg/m^2 | Time of MK-8776 Cmax (Tmax) | Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2) | 0.27 hr | Standard Deviation 0.02 |
| MK-8776 20mg/m^2+Gemcitabine 800mg/m^2 | Time of MK-8776 Cmax (Tmax) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 0.26 hr | Standard Deviation 0.01 |
| MK-8776 40mg/m^2+Gemcitabine 800mg/m^2 | Time of MK-8776 Cmax (Tmax) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 0.29 hr | Standard Deviation 0.06 |
| MK-8776 40mg/m^2+Gemcitabine 800mg/m^2 | Time of MK-8776 Cmax (Tmax) | Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2) | 0.35 hr | Standard Deviation 0.13 |
| MK-8776 80mg/m^2+Gemcitabine 800mg/m^2 | Time of MK-8776 Cmax (Tmax) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 0.24 hr | Standard Deviation 0.03 |
| MK-8776 80mg/m^2+Gemcitabine 800mg/m^2 | Time of MK-8776 Cmax (Tmax) | Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2) | 0.25 hr | Standard Deviation 0.06 |
| MK-8776 112mg/m^2+Gemcitabine 800mg/m^2 | Time of MK-8776 Cmax (Tmax) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 0.30 hr | Standard Deviation 0.08 |
| MK-8776 112mg/m^2+Gemcitabine 800mg/m^2 | Time of MK-8776 Cmax (Tmax) | Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2) | 0.28 hr | Standard Deviation 0.06 |
| MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2 | Time of MK-8776 Cmax (Tmax) | Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2) | 0.26 hr | Standard Deviation 0.03 |
| MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2 | Time of MK-8776 Cmax (Tmax) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 0.26 hr | Standard Deviation 0.05 |
| MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2 | Time of MK-8776 Cmax (Tmax) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 0.23 hr | Standard Deviation 0.02 |
| MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2 | Time of MK-8776 Cmax (Tmax) | Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2) | 0.23 hr | Standard Deviation 0.01 |
| MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2 | Time of MK-8776 Cmax (Tmax) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 0.48 hr | Standard Deviation 0.02 |
| MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2 | Time of MK-8776 Cmax (Tmax) | Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2) | 0.50 hr | — |
| MK-8776 200mg+Gemcitabine 1000mg/m^2 | Time of MK-8776 Cmax (Tmax) | Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2) | 0.57 hr | — |
| MK-8776 200mg+Gemcitabine 1000mg/m^2 | Time of MK-8776 Cmax (Tmax) | Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2) | 0.49 hr | — |